In silico pharmacology最新文献

{"title":"Unraveling <i>Grewia bilamellata</i> Gagnep. Role in cerebral ischemia: Comprehensive in vivo and <i>in silico</i> studies.","authors":"Poornima Gurivelli, Sunitha Katta","doi":"10.1007/s40203-024-00237-w","DOIUrl":"10.1007/s40203-024-00237-w","url":null,"abstract":"<p><p>The present study investigated the neuroprotective properties of whole plants of <i>Grewia bilamellata</i> Gagnep. extract (GBEE) against cerebral ischemia by harnessing both In vivo studies in a rat model and <i>In silico</i> studies focusing on nitric oxide synthase (NOS) inhibition. High-resolution liquid chromatography‒mass spectrometry (HR LC‒MS) analysis identified 32 phytochemicals in the GBEE, 15 of which adhered to Lipinski's rule of five. These compounds exhibited diverse physicochemical properties and high binding affinity to NOS, with cleomiscosin D showing the greatest potential. In vivo, GBEE had significant neuroprotective effects on bilateral common carotid artery occlusion/reperfusion (BCCAO/R) in rats, especially at doses of 200 mg/kg and 400 mg/kg body weight. GBEE treatment improved brain function, as evidenced by EEG normalization, substantial reductions in cerebral infarction size, mitigated neuronal loss, and the restoration of regular histological arrangement in the CA1 hippocampal area of the brain. Furthermore, GBEE enhanced antioxidant defenses by augmenting the activity of catalase (CAT) and superoxide dismutase (SOD), reducing malondialdehyde (MDA) levels, and restoring reduced glutathione (GSH) levels. These effects were accompanied by a decrease in nitric oxide (NO) levels, indicative of attenuated oxidative and nitrosative stress. Collectively, our findings suggest that GBEE is a promising natural therapeutic agent that may prevent or alleviate ischemic brain injury through a multifaceted mechanism involving NOS inhibition and attenuation of the oxidative stress response. This study highlights the therapeutic potential of GBEE and warrants further research into its mechanism of action and possible clinical applications.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"62"},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GC-MS analysis and pharmacological potentiality of <i>Lasia spinosa</i> (L.) Thwaites leaves and fruit extracts: an in vitro and in silico studies.","authors":"Md Anamul Haq, Md Eram Hosen, Rakhi Rani, Alomgir Hossain, Mahmudur Rahman, Md Sagor Ali, Rashed Zaman, Md Khalekuzzaman, Md Asadul Islam, Amti Kumar Dutta, Uzzal Kumar Acharjee","doi":"10.1007/s40203-024-00235-y","DOIUrl":"10.1007/s40203-024-00235-y","url":null,"abstract":"<p><p><i>Lasia spinosa</i> (<i>L. spinosa</i>) is widely used in Asian countries for treating various diseases and as a vegetable, yet its bioactive properties remain under-researched. It is traditionally utilized in Ayurveda and the AYUSH system of medicine for its medicinal properties, and commonly used to treat digestive disorders, respiratory issues, and inflammatory conditions. This study aims to identify the phytochemicals in <i>L. spinosa</i> leaves and fruit extracts and evaluate their biological activities. Phytochemicals in methanol extracts of <i>L. spinosa</i> fruits and leaves were identified by GC-MS analysis. Antioxidant and cytotoxic activities were assessed using the DPPH free radical and nitric oxide (NO) scavenging assay and brine shrimp lethality test. Antibacterial activity was evaluated against <i>Shigella boydii</i>, <i>Shigella flexneri</i>, <i>Streptococcus iniae</i>, <i>and Streptococcus dysgalactiae</i>, while antifungal properties were tested against <i>Cercospora beticola and Rhizoctonia solani</i>. Molecular docking was conducted to predict the effectiveness of <i>L. spinosa</i> phytochemicals against NADPH oxidase and the <i>Shigella</i> effector OspG. Nine compounds were detected from both extracts. The methanol leaves extract exhibited superior antioxidant activity compared to the fruit extract, with IC₅₀ values of 111.81 ± 8.99 µg/ml and 174.81 ± 4.86 µg/ml, respectively, as determined by the DPPH scavenging assay. The nitric oxide (NO) scavenging assay also revealed higher potency in the leaves extract (IC₅₀ = 138.59 ± 1.50 µg/ml) compared to the fruit extract (IC₅₀ = 196.47 ± 1.72 µg/ml). Both extracts showed significant antimicrobial activity against all tested microorganisms. In silico studies indicated notable inhibitory activity of all phytochemicals against the target proteins, with Linoelaidic acid and 9-Octadecenamide, (Z)- exhibiting the highest activity against NADPH oxidase (PDB: 2cdu) and <i>Shigella flexneri</i> OspG effector kinase (PDB: 4bvu), respectively. These findings suggest that <i>L. spinosa</i> has potent antioxidant and antimicrobial activities. Compounds from this plant could serve as lead compounds for developing antioxidant and antibacterial agents. However, molecular studies should be addressed.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"61"},"PeriodicalIF":0.0,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing of Drug Bank Compounds against <i>Plasmodium falciparum</i> Dihydroorotate Dehydrogenase as novel anti malarial drug candidates by Computational approaches.","authors":"Priyanka Joshi, Pankaja Pandey, Shilpi Rawat, Subhash Chandra","doi":"10.1007/s40203-024-00232-1","DOIUrl":"10.1007/s40203-024-00232-1","url":null,"abstract":"<p><p>This study aimed to repurpose Drug Bank Compounds against <i>P. falciparum</i> Dihydroorotate dehydrogenase (Pf-DHODH)a potential molecular target for antimalarial drug development due to its vital role in <i>P. falciparum</i> survival. Initially, the MATGEN server was used to screen drugs against Pf-DHODH (PDB ID 6GJG), followed by revalidating the results through docking by Autodock Vina through PyRx. Based on the docking results, three drugs namely, Talnifumate, Sulfaphenazole, and (3S)-N-[(2S)-1-[2-(1H-indol-3-yl)ethylamino]-1-oxopropan-2-yl]-1-(4-methoxyphenyl)-5-oxopyrrolidine-3-carboxamide-were subjected to molecular dynamics simulation for 100 ns. Molecular dynamics simulation results indicate that (3S)-N-[(2S)-1-[2-(1H-indol-3-yl)ethylamino]-1-oxopropan-2-yl]-1-(4-methoxyphenyl)-5-oxopyrrolidine-3-carboxamide- and Sulfaphenazole may target Pf-DHODH by forming a stable protein-ligand complex as they showed better free binding energy -130.58 kJ/mol, and -79.84 kJ/mol, respectively as compared to the free binding energy 116.255 kJ/mol of the reference compound; 3,6-dimethyl- ~ {N}-[4-(trifluoromethyl)phenyl]-[1,2]oxazolo[5,4-d]pyrimidin-4-amine. Although the studied compounds are drugs, still we applied Lipinski's rules and ADMET analysis that reconfirmed that these drugs have favorable drug-like properties. In conclusion, the results of the study show that Talniflumate and Sulfaphenazole may be potential antimalarial drug candidates.The derivatives of these drugs could be designed and tested to develop better drugs against Plasmodium species.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"60"},"PeriodicalIF":0.0,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACE inhibitors from <i>Suaeda salsa</i>: 3D-QSAR modeling, metabolomics, molecular docking and molecular dynamics simulations.","authors":"Guanhua Yue, Heze Gu, Kuocheng Zhang, YuanLong Song, Yangguang Hao","doi":"10.1007/s40203-024-00233-0","DOIUrl":"10.1007/s40203-024-00233-0","url":null,"abstract":"<p><p>Inhibition of ACE is considered as one of the main strategies to reduce hypertension. ACE inhibitors derived from <i>Suaeda salsa</i> (<i>S. salsa</i>) present a novel antihypertensive agent source. This study employed 3D-QSAR pharmacophore, metabolomics, docking-based screening, and molecular dynamics simulations to identify ACE inhibitors from <i>S. salsa</i>. A set of 53 known molecules was chemically diverse to construct a 3D-QSAR model for predictive purposes. <i>S. salsa</i> was characterized using UPLC-QqQ-MS/MS and UPLC-Q-TOF-LC-MS techniques, 211 and 586 kinds of bioactive metabolites were identified, respectively. A total of 680 compounds were collected for database construction and virtual screening. An ADMET assessment was conducted to evaluate drug-likeness and pharmacokinetics parameters. Moreover, molecular docking results show that six top hit compounds bind to ACE tightly. Specially, diosmin could interact with ACE by hydrogen bond, Pi-cation bond, and metal bond. Molecular dynamics (MD) simulation and MMPBSA calculations were subsequently employed to elucidate complex stability and the interaction between diosmin and ACE, indicating it a strong ACE inhibitory activity. In conclusion, this study suggests that <i>S.salsa</i> represents a potential source of antihypertensive agents.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00233-0.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"59"},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11192713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The combination of Curcumin and Doxorubicin on targeting PI3K/AKT/mTOR signaling pathway: an in vitro and molecular docking study for inhibiting the survival of MDA-MB-231.","authors":"Esha Sarkar, Akanksha Kotiya, Afreen Khan, Rajabrata Bhuyan, Syed Tasleem Raza, Aparna Misra, Abbas Ali Mahdi","doi":"10.1007/s40203-024-00231-2","DOIUrl":"10.1007/s40203-024-00231-2","url":null,"abstract":"<p><p>The process of tumorigenesis is highly associated with the disruption of cell-cycle regulators and derangement of various signaling pathways, which end up with the inhibition of apoptosis and hyper-activation of survival pathways. The PI3K medicated AKT/mTOR pathway is the widely explained mechanism for cancer cell survival which causes the overexpression of MDM2 and downregulates the p53-BAX mediated apoptotic pathway. Curcumin (CUR), the phyto-compound, derived from <i>Curcuma longa</i> is currently being focused on for its anticancer activities against breast cancer cells, MDA-MB-231, not only because of its minimal cytotoxicity against healthy cells (HEK293) but also because it synergistically sensitizes the activity of Doxorubicin (DOXO) in lower doses, which can be a promising source for complementary drug development. This study aims to investigate the combinatorial effect of CUR and DOXO on PI3K/AKT/mTOR pathway proteins by sequential molecular docking analysis and MD simulation studies. The lower binding affinity of the sequentially docked protein-ligand complex proves the increasing binding affinity of CUR and DOXO in the combinatorial dose. The mRNA expressions of different genes of this pathway are observed and quantified using rt-qPCR, where the decreasing fold change (2^-∆∆Ct) indicates the suppression of the AKT/mTOR pathway after co-treatment of CUR and DOXO against MDA-MB-231 cells. These in silico and in vitro findings can be a new horizon for further in vitro and clinical trials of breast cancer treatment.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00231-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 2","pages":"58"},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11192715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular docking of antidiabetic molecules of libas (<i>Spondias pinnata</i>) fruit and prediction of their pharmacokinetic properties.","authors":"Joy Elaine K Diacos","doi":"10.1007/s40203-024-00230-3","DOIUrl":"10.1007/s40203-024-00230-3","url":null,"abstract":"<p><p>Diabetes mellitus is one of the chronic metabolic disorders that affects more than 16 million Filipinos. Proper education, medical intervention, and a good lifestyle can help individuals control and manage this disease. <i>Spondias pinnata</i> is one of the underutilized crops in the Philippines that is well-known for its satisfactory flavor and medicinal properties, including its antidiabetic activity. The quest for a natural and effective drug to manage diseases is a continuous work in progress. Drug discovery and design is a tedious and expensive process. Computer-aided drug design guides the design and makes the process more efficient and less costly. Molecular docking was used to determine the potential antidiabetic compounds from the 48 reported compounds found in <i>S. pinnata</i> fruit. Seven compounds namely squalene (-9.1 kcal/mol), rutin (-9 kcal/mol), catechin (-8.7 kcal/mol), quercetin (-8.5 kcal/mol), tocopherol (-8.4 kcal/mol), myricetin (-8.4 kcal/mol), and ellagic acid (-8.3 kcal/mol) showed binding affinities comparable to those of pioglitazone, a standard drug, with peroxisome proliferator-activated receptor gamma (PPARγ). Tocopherol and catechin showed good ADMET properties. Among the two compounds, catechin passed the four filters for drug-likeness. Thus, catechin could be a potential compound for the development of antidiabetic drugs.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00230-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"57"},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11178756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141332748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring gene network and protein interaction analysis of neurotrophin signaling pathway in ameloblastoma.","authors":"Sidhra Syed Zameer Ahmed, Manimaran Vetrivel, Syed Zameer Ahmed Khader, Yoithapprabhunath Thuckanaickenpalayam Ragunathan, SriChinthu Kenniyan Kumar, Puniethaa Prabhu, Dharani Lakshmi Devi Rajaram","doi":"10.1007/s40203-024-00223-2","DOIUrl":"10.1007/s40203-024-00223-2","url":null,"abstract":"<p><p>Ameloblastoma is a non-cancerous but aggressive oral tumor emerging from odontogenic epithelial tissue involved during odontogenesis. Since there is lack in unravelling the complete molecular pathogenesis of ameloblastoma, chemotherapy is less attempted and a lot of disagreement over the optimal treatment option. Hence, till date, wide surgical resection is considered to be the reliable treatment for ameloblastoma. The Neurotrophin Signaling pathway plays an important role in neuron signaling and it is closely related with the MAPK pathway, which on the other hand regulated cell differentiation, apoptosis, proliferation, plasticity and survival. Protein- Protein Interaction analysis was analysed with STRING tool using WNL value, identified that CTNNB1, HRAS, NGFR, NGFR, and SORT1 having high interacting with BDNF, NT4, p75NTR, NGF, and NT3. The results of ontology analysis revealed that Neurotrophin signaling pathway is associated with Cell surface receptor signaling pathway, regulation of cell differentiation, regulation of development process, EGFR tyrosine kinase inhibitor resistance, MAPK signaling pathway, PI3K-Akt signaling pathway and Ras signaling pathway leading to pathogenesis involving genes. Further, clustering coefficient values of proteins BDNF, NT4, p75NTR, NGF & NT3 were identified as 0.627, 0.708, 0.367, 0.644 & 0.415<i>.</i> The results of molecular docking studies revealed among the selected ligands Methyl-ɣ-oresellinate, N-(4-Hydroxy-phenyl)-2-phenyl-N-phenylacetyl-acetamide, Atranorin and Oresellinate exhibited high binding affinity with selected protein. The key genes involved in Neurotrophin signaling pathway leading to ameloblastoma pathogenesis is revealed, which are closely associated with cell differentiation, cell proliferation, pro-apoptosis, and pro-survival regulations. Further it can be concluded that Neurotrophin signaling pathway could be one of the promising pathway to tailor the targeted drug therapy for Ameloblastoma treatment.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00223-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"56"},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11164846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico bioprospecting of receptors associated with the mechanism of action of Rondonin, an antifungal peptide from spider <i>Acanthoscurria rondoniae</i> haemolymph.","authors":"Elias Jorge Muniz Seif, Marcelo Yudi Icimoto, Pedro Ismael Silva Júnior","doi":"10.1007/s40203-024-00224-1","DOIUrl":"10.1007/s40203-024-00224-1","url":null,"abstract":"<p><p>Multiple drug-resistant fungal species are associated with the development of diseases. Thus, more efficient drugs for the treatment of these aetiological agents are needed. Rondonin is a peptide isolated from the haemolymph of the spider <i>Acanthoscurria rondoniae</i>. Previous studies have shown that this peptide has antifungal activity against <i>Candida</i> sp. and <i>Trichosporon</i> sp. strains, acting on their genetic material. However, the molecular targets involved in its biological activity have not yet been described. Bioinformatics tools were used to determine the possible targets involved in the biological activity of Rondonin. The PharmMapper server was used to search for microorganismal targets of Rondonin. The PatchDock server was used to perform the molecular docking. UCSF Chimera software was used to evaluate these intermolecular interactions. In addition, the I-TASSER server was used to predict the target ligand sites. Then, these predictions were contrasted with the sites previously described in the literature. Molecular dynamics simulations were conducted for two promising complexes identified from the docking analysis. Rondonin demonstrated consistency with the ligand sites of the following targets: outer membrane proteins F (id: 1MPF) and A (id: 1QJP), which are responsible for facilitating the passage of small molecules through the plasma membrane; the subunit of the flavoprotein fumarate reductase (id: 1D4E), which is involved in the metabolism of nitrogenous bases; and the ATP-dependent Holliday DNA helicase junction (id: 1IN4), which is associated with histone proteins that package genetic material. Additionally, the molecular dynamics results indicated the stability of the interaction of Rondonin with 1MPF and 1IN4 during a 10 ns simulation. These interactions corroborate with previous in vitro studies on Rondonin, which acts on fungal genetic material without causing plasma membrane rupture. Therefore, the bioprospecting methods used in this research were considered satisfactory since they were consistent with previous results obtained via in vitro experimentation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00224-1.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"55"},"PeriodicalIF":0.0,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141307689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical analysis, physicochemical, pharmacokinetic properties and molecular docking studies of bioactive compounds in <i>Ottelia alismoides</i> (L.) pers. Against breast cancer proteins.","authors":"Sathish Muthukrishnan, Suriya Sekar, Chamundeeswari Raman, Jeevan Pandiyan, Jansirani Ponnaiah","doi":"10.1007/s40203-024-00227-y","DOIUrl":"10.1007/s40203-024-00227-y","url":null,"abstract":"<p><p>Plants provide compounds that can be used to treat diseases, and <i>in silico</i> methods help to expedite drug discovery while reducing costs. This study explored the phytochemical profile of methanol extract of <i>O. alismoides</i> using GC-MS to identify potential bioactive compounds. Autodock 4.2.6. was employed for molecular docking evaluation of the efficacy of these identified compounds against Estrogen Receptor Alpha (ERα), Human Epidermal Growth Factor Receptor 2 (HER2), and Epidermal Growth Factor Receptor (EGFR), proteins. Additionally, the ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of the compounds were predicted using the SwissADME online tool. The preliminary phytochemical analysis revealed the presence of alkaloids, carbohydrates, glycosides, and steroids. During the GC-MS analysis, seven compounds were identified, and drug-likeness prediction of these compounds showed good pharmacokinetic properties having high gastrointestinal absorption, and orally bioavailable. The molecular docking studies exhibited promising binding affinities of bioactive compounds against all target proteins. Specifically, the compounds Tricyclo[5.2.1.0(2,6)]decan-10-ol and 2,2,6-Trichloro-7-oxabicyclo[4.1.0]heptane-1-carboxamide demonstrated the highest binding affinities with the ERα (-6.3 and - 6.0 k/cal), HER2 (-5.6 and - 6.1 k/cal), and EGFR (-5.4 and - 5.4 k/cal), respectively. These findings suggest the potential of <i>O. alismoides</i> as a source for developing new cancer therapeutics. The study highlights the effectiveness of <i>in silico</i> approaches for accelerating drug discovery from natural sources and paves the way for further exploration of these promising compounds.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00227-y.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"53"},"PeriodicalIF":0.0,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of molecular interactions of pesticides with keratinase for their potential to inhibit keratin biodegradation.","authors":"Indira Gahatraj, Rubina Roy, Anupama Sharma, Banashree Chetia Phukan, Sanjeev Kumar, Diwakar Kumar, Piyush Pandey, Pallab Bhattacharya, Anupom Borah","doi":"10.1007/s40203-024-00229-w","DOIUrl":"10.1007/s40203-024-00229-w","url":null,"abstract":"<p><p>The recalcitrant, fibrous protein keratin is found in the outermost layer of vertebrate skin, feathers, hair, horn, and hooves. Approximately, 10 million tons of keratin wastes are produced annually worldwide, of which around 8.5 million tons are from feather wastes. The biodegradation of keratin has been a challenge due to the lack of understanding of biological parameters that modulate the process. Few soil-borne microbes are capable of producing keratinase enzyme which has the potential to degrade the hard keratin. However, various pesticides are abundantly used for the management of poultry farms and reports suggest the presence of the pesticide residues in feather. Hence, it was hypothesized that pesticides would interact with the substrate-binding or allosteric sites of the keratinase enzyme and interferes with the keratin-degradation process. In the present study, molecular interactions of 20 selected pesticides with the keratinase enzyme were analyzed by performing molecular docking. In blind docking, 14 out of 20 pesticides showed higher inhibitory potential than the known inhibitor phenylmethylsulfonyl flouride, all of which exhibited higher inhibitory potential in site-specific docking. The stability and strength of the protein complexes formed by the top best potential pesticides namely fluralaner, teflubenzuron, cyhalothrin, and cyfluthrin has been further validated by molecular dynamic simulation studies. The present study is the first report for the preliminary investigation of the keratinase-inhibitory potential of pesticides and highlights the plausible role of these pesticides in hindering the biological process of keratin degradation and thereby their contribution in environmental pollution.</p><p><strong>Graphical abstract: </strong>Illustration depicting the hypothesis, experimental procedure, and the resultant keratinase-inhibitory potential of selected pesticides.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"54"},"PeriodicalIF":0.0,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}